The analysis of mitochondrial DNA mutation in seven Chinese families with Leber's hereditary optic neuropathy

Objective To observe the molecular genetic characteristics of seven Chinese families with Leber's hereditary optic neuropathy (LHON).Methods Ophthalmologic examinations were performed on seven probands,maternal members from seven Chinese families and 134 healthy controls.There were two LHON patients in seven Chinese families except probands.The entire mitochondrial genome was amplified using 24 pairs of oligonucleotide primers with overlapping fragments.The mutational site was analyzed through comparison of the results and Cambridge reference sequence.The penetrance of mutation site was calculated and the haplotype was analyzed.Results Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated with ND4 G11778A,ND1 G3460A and ND6 T14484C mutations.The ND1 T3394C mutation in probands and other matrilineal relatives was present in four out of 134 Chinese healthy controls.Strikingly,these families exhibited very low penetrance of visual impairment.The penetrance was 12.50％,22.22％,16.76％,6.25％,9.09％,11.11％ and 28.57％.The results of phylogenetic tree analysis of submitochondrial haplotype showed that these mtDNA polymorphism sites belong to the Asian haplogroups M9,M9,M,D4,M,M9 and M9.Conclusions T3394C mutation exists in seven Chinese LHON pedigrees,and the penetrance was ranged from 6.25％ to 28.57％.The patients have different clinical manifestations. Key words: Optic atrophy, hereditary, Leber/etiology ;  DNA, nitochondrial ;  Mutation